TY  - JOUR
A1  - Zielen, Stefan
A1  - Dücker, Ruth Pia
A1  - Wölke, Sandra
A1  - Donath, Helena
A1  - Bakhtiar, Shahrzad
A1  - Bücker, Aileen
A1  - Kreyenberg, Hermann
A1  - Hünecke, Sabine
A1  - Bader, Peter
A1  - Mahlaoui, Nizar
A1  - Ehl, Stephan
A1  - El-Helou, Sabine M.
A1  - Pietrucha, Barbara
A1  - Plebani, Alessandro
A1  - Flier, Michiel van der
A1  - Aerde, Koen van
A1  - Kilic, Sara S.
A1  - Reda, Shereen M.
A1  - Kostyuchenko, Larysa
A1  - McDermott, Elizabeth
A1  - Galal, Nermeen
A1  - Pignata, Claudio
A1  - Pérez, Juan Luis Santos
A1  - Laws, Hans-Jürgen
A1  - Niehues, Tim
A1  - Kutukculer, Necil
A1  - Seidel, Markus
A1  - Marques, Laura
A1  - Ciznar, Peter
A1  - Edgar, John David M.
A1  - Soler-Palacín, Pere
A1  - Bernuth, Horst von
A1  - Krüger, Renate
A1  - Meyts, Isabelle
A1  - Baumann, Ulrich
A1  - Kanariou, Maria
A1  - Grimbacher, Bodo
A1  - Hauck, Fabian
A1  - Graf, Dagmar
A1  - Gonzalez Granado, Luis Ignacio
A1  - Prader, Seraina Olivia
A1  - Reisli, Ismail
A1  - Slatter, Mary
A1  - Rodríguez-Gallego, Carlos
A1  - Arkwright, Peter D.
A1  - Bethune, Claire
A1  - Deripapa, Elena
A1  - Sharapova, Svetlana O.
A1  - Lehmberg, Kai
A1  - Davies, E. Graham
A1  - Schütz, Catharina
A1  - Kindle, Gerhard
A1  - Schubert, Ralf
T1  - Simple measurement of IgA predicts immunity and mortality in Ataxia-Telangiectasia
T2  - Journal of clinical immunology
N2  - Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)
KW  - Ataxia-telangiectasia
KW  - IgA deficiency
KW  - Immunoglobulins
KW  - Immunodeficiency
KW  - Lymphopenia Mortality
KW  - Mortality
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63573
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-635730
SN  - 1573-2592
N1  - Open Access funding enabled and organized by Projekt DEAL. The ESID Registry was supported by the German Federal Ministry of Education and Research (BMBF 01GM0896, 01GM1111B, 01GM1517C, 01EO1303 and 01ZZ1801B) EU grant no. HEALTH-F2-2008–201549 (EURO-PADnet), the pharmaceutical companies Novartis, GlaxoSmithKline, LFB, and UCB UK, the Plasma Protein Therapeutics Association (PPTA), the Care-for-Rare Foundation, PROimmune e.V, LFB, and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2155 RESIST—Project ID 39087428. EGD is supported by the UK National Institute of Health Research and the Great Ormond Street Hospital Biomedical Research Centre.
VL  - 41
SP  - 1878
EP  - 1892
PB  - Springer Science + Business Media B.V
CY  - Dordrecht [u.a.]
ER  -